Project Summary/Abstract Dr. Matthew B. Bevers is a neurologist in the divisions of Stroke, Cerebrovascular, and Critical Care Neurology at Brigham and Women's Hospital (BWH) whose goal is to become an independent investigator with expertise in mechanisms of secondary brain injury after intracerebral hemorrhage (ICH). His career development plan leverages the resources of a world-class training environment by bringing together a team of mentors and collaborators at a leading academic institution, Harvard Medical School, including both BWH and the Massachusetts General Hospital. Dr. Bevers has already obtained preliminary results supporting a role for the IL33/ST2 pathway in the pathophysiology of intracerebral hemorrhage and demonstrating the feasibility of his proposed studies into its role in the development of perihematomal edema and regulation of T cell and monocyte populations. Under the primary mentorship of Dr. W. Taylor Kimberly at MGH with a mentorship committee including Drs. Page Pennell and Francisco Quintana at BWH and scientific advisors including Drs. Lauren Sansing and Kevin Sheth at Yale University, Dr. Bevers proposes: 1) To identify a link between increases in a regulator of immune cell function ? soluble ST2 ? and perihematomal edema and functional outcome after ICH and 2) to identify changes in populations of immune effector cells associated with elevated sST2 and 3) to show the effect of manipulating the ST2/IL33 system on those immune cells. The overall goal of this project is to begin to explore a mechanistic pathway by which the initial injury from intracerebral hemorrhage leads to initiation of cerebral edema and ultimate neurologic outcome. By bringing together novel conceptual and technical approaches to the study of brain edema and immunology, this project will generate new insights into mechanisms of secondary brain injury. In the long term, Dr. Bevers' career goal is to identify unique molecular targets and develop novel therapies to improve neurologic recovery after hemorrhagic stroke. The proposed patient-oriented research project, along with mentorship and structured career development and scientific training, will provide Dr. Bevers with the skills and experience needed to become an independent investigator in the field of acute neurovascular injury.